Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60

2018 ◽  
Vol 25 (5) ◽  
pp. 699-708 ◽  
Author(s):  
Le H Hua ◽  
Tracey H Fan ◽  
Devon Conway ◽  
Nicolas Thompson ◽  
Tyler G Kinzy
Keyword(s):  
Multiple Sclerosis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Clinical Relapse ◽  
Real World Data ◽  
Disease Modifying Therapy ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Patient Health ◽  
Disease Modifying

Background: The risk–benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. Objective: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients. Methods: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy. Pre- and post-discontinuation comparisons of Performance Scales (PS), Timed 25-Foot Walk, and Patient Health Questionnaire-9 (PHQ9) were analyzed using linear mixed models. Results: A total of 600 patients were included, with 178 (29.7%) discontinuing. Discontinuers were 2.2 years older, had 3.2 years longer disease duration, and 1.6 years lesser treatment exposure. Providers initiated discontinuation more than patients (68.0%). Only one clinical relapse occurred in discontinuers. A proportion (10.7%) reinitiated DMT. Provider-initiated discontinuers restarted less often (hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.12–0.9). In discontinuers, relapsing-remitting patients had lower PS on average than primary progressive. Provider-initiated discontinuation was associated with lower PS than patient- initiated discontinuation. PHQ9 scores appeared higher in those stopping intravenous (IV) therapies than interferons. Lower PS and PHQ9 indicate better outcomes. Conclusion: Most patients over age 60, who discontinued DMT, remained off DMT. This study provides real-world data that may guide clinicians considering discontinuing DMT.

scholarly journals CLICK-MS and MASTER-2 Phase IV trial design: cladribine tablets in suboptimally controlled relapsing multiple sclerosis

2021 ◽  
Author(s):  
Augusto A Miravalle ◽  
Joshua Katz ◽  
Derrick Robertson ◽  
Brooke Hayward ◽  
Danielle E Harlow ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Patient Reported Outcomes ◽  
Real World Data ◽  
Disease Modifying Drugs ◽  
Secondary Progressive ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Registration Number ◽  
Disease Modifying ◽  
Phase Iv

Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) are approved for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS and active secondary progressive MS. However, real-world data on cladribine tablets are limited. CLICK-MS and MASTER-2 are single arm, observational, 30-month, Phase IV studies in the US evaluating the effectiveness and safety of cladribine tablets 3.5 mg/kg in patients with relapsing-remitting MS or active secondary progressive MS who had suboptimal response to prior injectable (CLICK-MS), or infusion/oral (MASTER-2) disease-modifying therapy. The primary end point is 24-month annualized relapse rate. Key secondary end points include patient-reported outcomes on quality of life measures, treatment adherence and adverse events. Studies began in 2019 and are expected to be completed in 2023. Trial registration number • CLICK-MS: NCT03933215 (ClinicalTrials.gov) Full title; CLadribine tablets: observational evaluation of effectIveness and patient-reported outcomes in suboptimally Controlled patients previously taKing injectable disease-modifying drugs for relapsing forms of Multiple Sclerosis • MASTER-2: NCT03933202 (ClinicalTrials.gov) Full title; Cladribine tablets: observational evaluation of effectiveness and patient-reported outcomes in suboptiMAlly controlled patientS previously Taking oral or infusion disEase-modifying dRugs for relapsing forms of multiple sclerosis

scholarly journals Fatigue at enrollment predicts EDSS worsening in the New York State Multiple Sclerosis Consortium

2018 ◽  
Vol 26 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Caila B Vaughn ◽  
Katelyn S Kavak ◽  
Michael G Dwyer ◽  
Aisha Bushra ◽  
Muhammad Nadeem ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
New York ◽  
Proportional Hazards ◽  
New York State ◽  
Cox Proportional Hazards ◽  
Common Symptom ◽  
York State ◽  
Study Enrollment ◽  
Severe Fatigue ◽  
Patient Reported

Background: Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). Objective: The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. Methods: In this retrospective cohort study of New York State MS Consortium (NYSMSC) registry, MS patients reporting moderate-to-severe fatigue at study enrollment ( n = 2714) were frequency matched to less-fatigued subjects ( n = 2714) on age, baseline Kurtzke Expanded Disability Status Scale (EDSS), disease duration, and MS phenotype. Change from baseline patient-reported outcomes (PROs), as measured by LIFEware™, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data ( n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. Results: The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2–10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2–1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all ps ⩽ 0.01). Conclusion: In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC.

scholarly journals Patient-Reported Disease-Modifying Therapy Adherence in the Clinic: A Reliable Metric?

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731877789 ◽  
Author(s):  
Devon S Conway ◽  
Maria Cecilia Vieira ◽  
Nicolas R Thompson ◽  
Kaila N Parker ◽  
Xiangyi Meng ◽  
...  
Keyword(s):  
Regression Models ◽  
Patient Reported Outcomes ◽  
Patient Reporting ◽  
Lesion Formation ◽  
Logistic Regression Models ◽  
Disease Modifying Therapy ◽  
Patient Reported ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
The Relationship

Background Adherence to multiple sclerosis (MS) disease-modifying therapy (DMT) is commonly assessed through patient reporting, but patient-reported adherence is rarely studied. Objective To determine rates of DMT adherence reported from patient to clinician, reasons for nonadherence, and relationships between adherence and outcomes. Methods We identified relapsing–remitting MS patients on DMT for ≥3 months. DMT adherence was defined as taking ≥80% of doses. Linear and logistic regression models were created used to determine the association of baseline adherence with several patient reported outcomes and the timed 25-foot walk at 6 months, 1 year, 2 years, and 3 years after the index visit. Results The analysis included 1148 patients, of whom 501 had data at 6 months, 544 at 1 year, 331 at 2 years, and 247 at 3 years. Baseline adherence was 94.9% and overall adherence was 93.1%. Forgetting was the most common reason for missed doses. In the adjusted models, adherence was not associated with the outcomes. Conclusions Higher than expected adherence and a lack of association between adherence and outcomes suggests patient reported adherence may not be reliable. Further research is needed to clarify the relationship between patient-reported adherence and relapses or new lesion formation.

Progressive Cerebellar Ataxia After Natalizumab Treatment

2021 ◽  
pp. 65-68
Author(s):  
Michel Toledano
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Polyoma Virus ◽  
Resonance Imaging ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

A 47-year-old woman with a history of relapsing-remitting multiple sclerosis (MS) receiving natalizumab therapy sought a second opinion regarding a recent diagnosis of secondary progressive disease. She was first diagnosed with multiple sclerosis 8 years earlier. While taking natalizumab, she was monitored for the development of antibodies to JC polyoma virus. Nine months before our evaluation, anti-JC polyoma virus antibodies became positive, with an increased index of 1.1. Given sustained remission, she was continued on natalizumab with increased surveillance and a plan to switch to a different disease-modifying therapy after 24 months. Five months later she noted subacute onset of slurred speech and right upper extremity incoordination. Over the next 4 months she continued to have clinical decline. On examination she had moderate ataxic dysarthria and right greater than left appendicular ataxia. She relied on a wheelchair for transportation and required 1-person assist to stand. Reflexes were brisk with bilateral Babinski sign. This patient with relapsing-remitting multiple sclerosis on natalizumab had a new subacute progressive cerebellar syndrome without radiographic evidence of disease activity. Repeated magnetic resonance imaging showed worsening cerebellar atrophy, right sided greater than left sided, and evolving T2 hyperintensity in the brainstem without enhancement or mass effect. JC polyoma virus polymerase chain reaction was positive. The patient was diagnosed with JC polyoma virus granule cell neuronopathy. Natalizumab was discontinued, and she was treated with 4 of 5 planned cycles of plasma exchange. After her 4th cycle, worsening symptoms developed. Magnetic resonance imaging showed gadolinium enhancement in the brainstem supportive of immune reconstitution inflammatory syndrome. She received high-dose intravenous methylprednisolone followed by a prednisone taper. Her disability progression stabilized. JC polyoma virus central nervous system infection, 1 of several infections reported among treated patients with multiple sclerosis, occurs almost exclusively in immunosuppressed patients, including those receiving disease-modifying therapy for multiple sclerosis.

A case of immune-mediated encephalitis related to daclizumab therapy

2018 ◽  
Vol 25 (5) ◽  
pp. 750-753 ◽  
Author(s):  
Michael Devlin ◽  
Andrew Swayne ◽  
Martin Newman ◽  
Cullen O’Gorman ◽  
Helen Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Brain Biopsy ◽  
Disease Modifying Therapy ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Csf Examination

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Switching first-line disease-modifying therapy after failure: impact on the course of relapsing–remitting multiple sclerosis

2009 ◽  
Vol 15 (1) ◽  
pp. 50-58 ◽  
Author(s):  
A Gajofatto ◽  
P Bacchetti ◽  
B Grimes ◽  
A High ◽  
E Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Initial Therapy ◽  
First Line ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Options for non-responders to relapsing–remitting multiple sclerosis (RRMS) first-line disease-modifying therapies (DMT) are limited. We explored whether switching first-line DMT is effective. Methods Patients with RRMS who first received interferon-beta (IFNB) or glatiramer acetate (GA) were classified in three categories: DMT change because of suboptimal response, DMT change because of other reasons, and no DMT change during follow-up. Outcomes included annualized relapse rate (ARR) and relapse-free proportions. Results We identified 597 patients who initiated first-line DMT. For patients who did not change DMT ( n = 240), pre-DMT and on-DMT median ARR were 0.50 and 0 ( P < 0.0001). At 24 months, 76% (95%CI = 69–81%) of patients who did not change DMT were relapse-free. Of the 155 who switched because of suboptimal response, 101 switched to another first-line DMT. Median ARR pre-DMT, on first DMT and second DMT were: 0.50, 0.55, and 0.25 for switchers from IFNB to GA (IFNB/GA, n = 12) (pre-DMT versus first DMT: P = 0.92; first versus second DMT: P = 0.31); 0.90, 0.50, and 0 for switchers from GA to IFNB (GA/IFNB, n = 18; P = 0.19; P = 0.01); 0.50, 0.68, and 0 for switchers from an IFNB to another IFNB (IFNB/IFNB’, n = 71; P = 0.34; P = 0.02). Estimated relapse-free proportion after 24 months of treatment was 42% (95%CI=15–66%) during the period on IFNB versus 53% (95%CI = 17–80%) on GA for IFNB/GA ( P = 0.21); 12% (95%CI = 0–40%) on GA versus 87% (95%CI = 59–97%) on IFNB for GA/IFNB ( P = 0.001); and 41% (95%CI = 29–52%) on initial IFNB versus 67% (95%CI = 53–79%) on subsequent IFNB for IFNB/IFNB’ ( P = 0.0001). Conclusions Switching first-line DMT in patients with RRMS failing initial therapy may be effective in many cases.

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